In normal cells a large portion of newly synthesized heterogeneous nuclear RNA and precursor ribosomal RNA do not reach the cytoplasm. Nuclear ribonucleases play an essential part in carrying out this post-transcriptional process. Much evidence indicates that chemical carcinogens cause aberration in this process during the precancerous period. However, little is known about the activity of these enzymes when the cells are undergoing neoplastic transformation. We propose to investigate the effects of feeding an azo dye carcinogen and azo dye plus a known antagonist during the preneoplastic period, on the liver nuclear RNases to determine: 1. whether the effect is a transient or a gradual and persistent one, and 2. whether the antagonist can correct the changes. Specifically, we will examine the enzymes in the liver at intervals and their resulting hyperplastic nodules. Nuclei from each type of sample will be separated into hepatocyte and non-hepatocyte fractions. These will be further fractionated into nucleolar and nucleoplasmic fractions. The determinations to be performed include: 1. the activity and 2. the amount of the exo- and endoribonuclease, 3. whether the purified nuclear RNases can act efficiently on the nuclear RNA of the dye fed rats, 4. whether a specific nuclear RNase inhibitor is present and 5. whether the cytoplasmic inhibitor acts on the nuclear enzymes. Through these experiments it may be possible to evaluate the hypothesis that the RNase is involved at a critical step of carcinogenesis and, more directly, to reveal the mechanism by which the defective RNA transport may result from changes in the activity of these enzymes. If a change in RNase activity proves to be a critical step in liver carcinogenesis, then this information should be helpful in the search for therapeutic and prophylactic agents, and perhaps also serve as a tool for assessing the carcinogenic potential of other chemicals with which we come in contact.